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Biomedical subjects

J Berger

Publications and source records attributed to J Berger.

At least 91 records · Page 5Linked to original sources
PubMed2001

Asbestos exposure and malignant lymphomas--a review of the epidemiological literature.

There has been a significant number of case reports on the occurrence of lymphomas in people previously exposed to asbestos. This raises the question of whether corresponding results are available from analytical epidemiological studies. In the present review of the epidemiological literature, we describe the results of the six cohort and 16 case-control studies that - according to our research - were published up to 1999 and, directly or indirectly. shed light on the above question. In summarizing the results of these studies, we have distinguished between non-Hodgkin lymphoma (NHL), chronic lymphatic leukemia (CLL) and plasmocytoma/ multiple myeloma (MM). A causal relationship between asbestos exposure and the subsequent development of lymphomas cannot be derived from the available results. However, since quite a number of studies and the combined analysis indicate a (weakly) increased risk, this question should be considered directly in future epidemiological studies. Such studies should address separately the various sub-entities, employing the latest internationally agreed classification, and should also use the latest methods of quantifying exposure.

Asbestos↗
PubMed2001

Molecular epidemiology of tuberculosis among eight hospitals in New York City, 1996-1997.

OBJECTIVE: To determine the molecular epidemiology of tuberculosis isolated from patients cared for at eight hospitals scattered throughout New York City. MATERIALS AND METHODS: Cases of tuberculosis occurring in 1996 and 1997 at collaborating hospitals were identified, and demographic data were extracted from patient charts. All available isolates were analyzed by IS6110 for genetic relatedness. The molecular fingerprints were compared both to each other and to the larger repository of strains from New York City developed and maintained at the Public Health Research Institute. RESULTS: One hundred and eighty cases were fully characterized. Compared with New York City cases, study patients were more likely to be Asian and less likely to be non-Hispanic blacks. Overall, 97 (54%) of the cases were clustered with respect to other study strains or with respect to the other New York City isolates. Clustered strains were significantly more likely to be from non-Hispanic blacks or patients born in the United States. The largest cluster (n = 17) was the "W" strain previously associated with an outbreak of multidrug-resistant tuberculosis in New York City. In the current study, the majority of W strain isolates were fully drug-susceptible. CONCLUSIONS: High rates of genetically related tuberculosis continue to occur among patients in New York City, in spite of improved control of nosocomial outbreaks and dramatic decreases in the overall case rates. The use of molecular techniques to suggest patterns of transmission has become essential in developing and assessing routine tuberculosis control strategies.

Adult↗
PubMed2001

Epigenetic downregulation of the retinoic acid receptor-beta2 gene in breast cancer.

A growing body of evidence supports the hypothesis that the retinoic acid receptor beta2 (RAR-beta2) gene is a tumor suppressor gene which induces apoptosis and that the chemopreventive and therapeutic effects of retinoids are due to induction of RAR-beta2. During breast cancer progression, RAR-beta2 is reduced or even lost. It is known from studies of other tumor-suppressor genes that methylation of the 5'-region is the cause of loss of expression. Several groups demonstrated that this is also true for the RAR-beta2 in breast cancer by treating breast cancer cell lines with a demethylating agent and examining expression of the RAR-beta2 gene in response to a challenge with retinoic acid. Studies using sodium bisulfite genomic sequencing as well as methylation specific PCR showed that a number of breast cancer cell lines as well as breast cancer tissue showed signs of methylation. The RAR-beta2 gene was unmethylated in non-neoplastic breast tissue as well as in other normal tissues. A combination of retinoic acid with demethylating agents as well as with histone deacetylase inhibitors acts synergistically to inhibit growth. This review presents data that suggest that treatment of cancer patients with demethylating agents followed by retinoic acid may offer a new therapeutic modality. Both the time of commencement of chemoprevention and the choice of substances that are able either to prevent de novo methylation or to reverse methylation-caused gene silencing may be important considerations.

Base Sequence↗
PubMed2001

Genetic mapping with SNP markers in Drosophila.

Map-based positional cloning of Drosophila melanogaster genes is hampered by both the time-consuming, error-prone nature of traditional methods for genetic mapping and the difficulties in aligning the genetic and cytological maps with the genome sequence. The identification of sequence polymorphisms in the Drosophila genome will make it possible to map mutations directly to the genome sequence with high accuracy and resolution. Here we report the identification of 7,223 single-nucleotide polymorphisms (SNPs) and 1,392 insertions/deletions (InDels) in common laboratory strains of Drosophila. These sequence polymorphisms define a map of 787 autosomal marker loci with a resolution of 114 kb. We have established PCR product-length polymorphism (PLP) or restriction fragment-length polymorphism (RFLP) assays for 215 of these markers. We demonstrate the use of this map by delimiting two mutations to intervals of 169 kb and 307 kb, respectively. Using a local high-density SNP map, we also mapped a third mutation to a resolution of approximately 2 kb, sufficient to localize the mutation within a single gene. These methods should accelerate the rate of positional cloning in Drosophila.

Animals↗
PubMed2001

Epidemiology of acne in the general population: the risk of smoking.

BACKGROUND: Acne is a common skin disorder, but epidemiological data from the general population obtained by examination are scarce. Clinical experience suggests an association between smoking and acne, although confirmatory evidence from appropriate studies is lacking. OBJECTIVES: To determine the prevalence and demographic factors of acne in a general population sample and to investigate the association of smoking and acne on a qualitative and quantitative level. METHODS: In a cross-sectional study, 896 citizens (aged 1--87 years, median 42) of the City of Hamburg were dermatologically examined. The prevalence and severity of acne were recorded and further information on demographic variables, medical history, and alcohol and cigarette consumption were obtained by a standardized interview. RESULTS: According to the clinical examination, acne was present in 26.8% overall, and was more prevalent in men (29.9%) than women (23.7%) (odds ratio, OR 1.37, 95% confidence interval, CI 1.01--1.87). Prevalence followed a significant linear trend over age with peak prevalence between 14 and 29 years (P < 0.001). The reported age at onset was significantly lower in women than men (P = 0.015). According to multiple logistic regression analyses acne prevalence was significantly higher in active smokers (40.8%, OR 2.04, 95% CI 1.40--2.99) as compared with non-smokers (25.2%). A significant linear relationship between acne prevalence and number of cigarettes smoked daily was obtained (trend test: P < 0.0001). In addition, a significant dose-dependent relationship between acne severity and daily cigarette consumption was shown by linear regression analysis (P = 0.001). CONCLUSIONS: Smoking is a clinically important contributory factor to acne prevalence and severity.

Acne Vulgaris↗
PubMed2001

Involvement of N-acetylmuramyl-L-alanine amidases in cell separation and antibiotic-induced autolysis of Escherichia coli.

N-acetylmuramyl-L-alanine amidases are widely distributed among bacteria. However, in Escherichia coli, only one periplasmic amidase has been described until now, which is suggested to play a role in murein recycling. Here, we report that three amidases, named AmiA, B and C, exist in E. coli and that they are involved in splitting of the murein septum during cell division. Moreover, the amidases were shown to act as powerful autolytic enzymes in the presence of antibiotics. Deletion mutants in amiA, B and C were growing in long chains of unseparated cells and displayed a tolerant response to the normally lytic combination of aztreonam and bulgecin. Isolated murein sacculi of these chain-forming mutants showed rings of thickened murein at the site of blocked septation. In vitro, these murein ring structures were digested more slowly by muramidases than the surrounding murein. In contrast, when treated with the amidase AmiC or the endopeptidase MepA, the rings disappeared, and gaps developed at these sites in the murein sacculi. These results are taken as evidence that highly stressed murein cross-bridges are concentrated at the site of blocked cell division, which, when cleaved, result in cracking of the sacculus at this site. As amidase deletion mutants accumulate trimeric and tetrameric cross-links in their murein, it is suggested that these structures mark the division site before cleavage of the septum.

Anti-Bacterial Agents↗
PubMed2001

Fibrate induction of the adrenoleukodystrophy-related gene (ABCD2): promoter analysis and role of the peroxisome proliferator-activated receptor PPARalpha.

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease due to a defect in the ABCD1 (ALD) gene. ABCD1, and the two close homologues ABCD2 (ALDR) and ABCD3 (PMP70), are genes encoding ATP-binding cassette half-transporters of the peroxisomal membrane. As overexpression of the ABCD2 or ABCD3 gene can reverse the biochemical phenotype of X-ALD (reduced beta-oxidation of very-long-chain fatty acids), pharmacological induction of these partially redundant genes may represent a therapeutic approach to X-ALD. We previously reported that the ABCD2 and ABCD3 genes could be strongly induced by fibrates, which are hypolipidaemic drugs and peroxisome-proliferators in rodents. We provide evidence that the induction is dependent on peroxisome proliferator-activated receptor (PPARalpha) as both genes were not induced in fenofibrate-treated PPARalpha -/- knock-out mice. To further characterize the PPARalpha pathway, we cloned and analysed the promoter of the ABCD2 gene, the closest homologue of the ABCD1 gene. The proximal region (2 kb) of the rat promoter displayed a high conservation with the human and mouse cognate sequences suggesting an important role of the region in regulation of the ABCD2 gene. Classically, fibrate-induction involves interaction of PPARalpha with a response element (PPRE) characterized by a direct repeat of the AGGTCA-like motif. Putative PPRE motifs of the rat ABCD2 promoter were studied in the isolated form or in their promoter context by gel-shift assay and transfection of COS-7 cells. We failed to characterize a functional PPRE, suggesting a different mechanism for the PPARalpha-dependent regulation of the ABCD2 gene.

ATP Binding Cassette Transporter, Subfamily D↗
PubMed2001

Neurodevelopmental and behavioural characteristics in learning disabilities and attention deficit disorder.

Specific learning disability in childhood is frequently associated with attention deficit disorder. The distinction between children with and without such comorbidity is often difficult to make. Our aim was to delineate the neurocognitive and behavioural differences between children with specific learning disabilities, with and without attention deficit. Students diagnosed with learning disability, mean age 8.3, 1.4 SD (N-50), and students with learning disability and attention deficit disorder, mean age 8.7, 1.4 SD (N-50), were assessed. The Paediatric Early Elementary Examination and the Aggregate Neurobehavioural Student Health Education Review were administered and their scores as well as pattern of correlations within and between domains were analysed. Only few differences in neurocognitive functions between these groups were evident. Most neurocognitive domains were similarly intercorrelated in the two groups. However, recall was correlated with other neurocognitive domains only among the children with learning and attention deficits. A proportion of significant correlations between neurocognitive and behavioural domains was found among the children with learning disability and attention deficit disorder, but not among the children with learning disability only. It appears that while neurocognitive profiles are similar in these two groups, their interrelationship with behavioural patterns differ. These findings give support to the neurological origin of attention deficit disorder related behaviours among learning disabled children. Different interventions should therefore be considered for each of these entities.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Calibrated electro-optic E-field sensors for hyperthermia applications.

E-field measurements are an important task for the investigation of newly developed hyperthermia applicators as well as for online control of hyperthermia treatments. Compact and non-perturbing integrated optical E-field sensors based on LiNbO3 as well as optical E-field sensors based on infrared emitting diodes and light bulbs are suitable for nearfield measurements of hyperthermia antennas. In order to investigate their properties a calibration cell with transverse electromagnetic (TEM) waves has been constructed. By using this cell, calibration curves and directional patterns for all sensors have been measured. Due to the threshold behaviour of the IRED and light bulb sensor, only the LiNbO3 sensor is capable of measuring weak fields inside an applicator or a homogeneous phantom.

Biophysical Phenomena↗
PubMed2001

Leukodystrophies: recent developments in genetics, molecular biology, pathogenesis and treatment.

The combined application of recently developed techniques for genetic and biochemical analysis, neuroimaging and the ability to create animal models has led to remarkable advances in the field of leukodystrophy research. The present review focuses on recent developments in X-linked adrenoleukodystrophy, Alexanders disease, Canavans disease, metachromatic leukodystrophy, globoid cell leukodystrophy (Krabbes disease) and Pelizaeus-Merzbacher disease, and briefly discusses new data on six other rare inherited leukodystrophies. Of the leukodystrophies, 12 can now be diagnosed precisely using noninvasive techniques, and the molecular defect has been identified in nine of these. Disease incidence can be reduced through genetic counselling. Presymptomatic diagnosis provides an opportunity for therapeutic intervention. Study of animal models facilitates elucidation of pathogenic mechanisms and identifies pathways that could be targeted by future therapies.

Brain↗
PubMed2001

The depressed suicidal patient. Assessment and treatment.

Depressive disorders are associated with significant psychosocial impairment and disability. Depression should be thoroughly evaluated, as should current and past suicidality and potential risk factors for suicide. Mortality by suicide characterizes the course of major affective disorders in approximately 15% of those suffering from these illnesses. Several neurobiological correlates of suicidality have been discovered. Treatment of depression with suicidality may involve hospitalization, pharmacotherapy, electroconvulsive therapy, and psychotherapy. Special populations include children and adolescents, the elderly, medically ill patients, patients with comorbid personality disorders, and patients with comorbid substance abuse disorders. Clinicians encountering patients with depressive disorders should be proficient in the assessment and treatment of depression with suicidality.

Adult↗
PubMed2001

Serum response factor is required for immediate-early gene activation yet is dispensable for proliferation of embryonic stem cells.

Addition of serum to mitogen-starved cells activates the cellular immediate-early gene (IEG) response. Serum response factor (SRF) contributes to such mitogen-stimulated transcriptional induction of many IEGs during the G0-G1 cell cycle transition. SRF is also believed to be essential for cell cycle progression, as impairment of SRF activity by specific antisera or antisense RNA has previously been shown to block mammalian cell proliferation. In contrast, Srf(-/-) mouse embryos grow and develop up to E6.0. Using the embryonic stem (ES) cell system, we demonstrate here that wild-type ES cells do not undergo complete cell cycle arrest upon serum withdrawal but that they can mount an efficient IEG response. This IEG response, however, is severely impaired in Srf(-/-) ES cells, providing the first genetic proof that IEG activation is dependent upon SRF. Also, Srf(-/-) ES cells display altered cellular morphology, reduced cortical actin expression, and an impaired plating efficiency on gelatin. Yet, despite these defects, the proliferation rates of Srf(-/-) ES cells are not substantially altered, demonstrating that SRF function is not required for ES cell cycle progression.

Animals↗
PubMed2001

[A comparative study of the ocular tolerance of 3 timolol-based preparations: the influence of preservatives on ocular tolerance].

PURPOSE: Ophthalmic preparations can cause toxic ocular reactions, often associated with the use of preservatives. The aim of this study was to compare the ocular tolerance of three ophthalmic preparations based on timolol: a preservative free ophthalmic preparation (Timabak) and two other commercially available preserved preparations (Timoptol) and Timoptol LP). METHODS: The effect of repeatedly instilling eye drops for 28 days on rabbit eyes was assessed in vivo by mean of a confocal laser scanning ophthalmoscope. The corneal microlesions were selectively marked by fluorescein. RESULTS AND CONCLUSION: The overall results show the good ocular tolerance of the three tested products. However, a closer comparison between the products brought out differences in the extent of lesions among the tested products depending on their composition. Indeed the preservative free eye drops appeared better tolerated than the two preserved preparations.

Adrenergic beta-Antagonists↗
PubMed2000

Srf(-/-) ES cells display non-cell-autonomous impairment in mesodermal differentiation.

The serum response factor (SRF) transcription factor is essential for murine embryogenesis. SRF+(-/-) embryos stop developing at the onset of gastrulation, lacking detectable mesoderm. This developmental defect may reflect cell-autonomous impairment of SRF(-/-) embryonic cells in mesoderm formation. Alternatively, it may be caused by a non-cell-autonomous defect superimposed upon inappropriate provision of mesoderm-inducing signals to primitive ectodermal cells. We demonstrate that the ability of SRF(-/-) embryonic stem (ES) cells to differentiate in vitro into mesodermal cells is indeed impaired. However, this impairment can be modulated by external, cell-independent factors. Retinoic acid, but not dimethylsulfoxide, permitted activation of the mesodermal marker gene T(Bra), which was also activated when SRF was expressed in SRF(-/-) ES cells. Embryoid bodies from SRF(-/-) ES cell aggregates also activated mesodermal marker genes, but displayed unusual morphologies and impairment in cavitation. Finally, in nude mice, Srf(-/-) ES cells readily differentiated into mesodermal cells of SRF(-/-) genotype, including cartilage, bone or muscle cells. We demonstrate that SRF contributes to mesodermal gene expression of ES cells and that SRF(-/-) ES cells display a non-cell-autonomous defect in differentiation towards mesoderm.

Animals↗
PubMed2000

Co-expression of mutated and normal adrenoleukodystrophy protein reduces protein function: implications for gene therapy of X-linked adrenoleukodystrophy.

Inherited defects in the X-chromosomal adrenoleukodystrophy (ALD; ABCD1) gene are the genetic cause of the severe neurodegenerative disorder X-linked adrenoleukodystrophy (X-ALD). Biochemically the accumulation of very long-chain fatty acids, caused by impaired peroxisomal beta-oxidation, is the pathognomonic characteristic of the disease. Due to the X-chromosomal inheritance of X-ALD no data are available to clarify the question whether mutated adrenoleukodystrophy proteins (ALDPs) can negatively influence normal ALDP function. Here we show that restoration of beta-oxidation in X-ALD fibroblasts following transient transfection with normal ALD cDNA is more effective in ALDP-deficient fibroblasts compared with fibroblasts expressing normal amounts of mutated ALDP. Furthermore, we utilized the HeLa Tet-on system to construct a stable HeLa cell line expressing a constant level of endogenous ALDP and doxycycline-inducible levels of mutated ALDP. The induction was doxycycline dosage-dependent and the ALDP correctly localized. Interestingly, although mutated ALDP increased >6-fold in a dosage-dependent manner the total amount of ALDP (mutated and normal) remained approximately even as demonstrated by western blot and flow cytometric analyses. Thus, apparently mutated and normal ALDP compete for integration into a limited number of sites in the peroxisomal membrane. Consequently, increased amounts of mutated ALDP resulted in decreased peroxisomal beta-oxidation and accumulation of very long-chain fatty acids. These findings have direct implications on future gene therapy approaches for treatment of X-ALD, since in some patients a non-functional endogenous protein could act in a dominant negative way or displace the introduced, normal protein.

ATP Binding Cassette Transporter, Subfamily D, Mem↗